IL122462A - Preparation of triazoles by organometallic metal attachment to ketones and a number of such new compounds - Google Patents

Preparation of triazoles by organometallic metal attachment to ketones and a number of such new compounds

Info

Publication number: IL122462A
Authority: IL; Israel
Prior art keywords: compound; formula; chloro; acid addition; difluorophenyl
Prior art date: 1995-08-05

Application number

IL12246296A

Other languages

English (en)

Hebrew (he)

Other versions

IL122462A0 (en

Original Assignee

Pfizer Res & Dev

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1995-08-05

Filing date

1996-07-26

Publication date

2001-10-31

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=10778850&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=IL122462(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1996-07-26 Application filed by Pfizer Res & Dev filed Critical Pfizer Res & Dev

1996-07-26 Priority to IL13152196A priority Critical patent/IL131521A/en

1998-06-15 Publication of IL122462A0 publication Critical patent/IL122462A0/xx

2001-10-31 Publication of IL122462A publication Critical patent/IL122462A/en

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 110
238000002360 preparation method Methods 0.000 title claims abstract description 42
150000002576 ketones Chemical class 0.000 title description 8
150000003852 triazoles Chemical class 0.000 title description 2
125000002524 organometallic group Chemical group 0.000 title 1
238000006243 chemical reaction Methods 0.000 claims abstract description 82
238000000034 method Methods 0.000 claims abstract description 58
150000003839 salts Chemical class 0.000 claims abstract description 52
239000002253 acid Substances 0.000 claims abstract description 44
BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 claims abstract description 34
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 30
229910052740 iodine Inorganic materials 0.000 claims abstract description 30
239000011630 iodine Substances 0.000 claims abstract description 30
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims abstract description 27
125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 23
125000001246 bromo group Chemical group Br* 0.000 claims abstract description 18
229910052725 zinc Inorganic materials 0.000 claims abstract description 16
239000011701 zinc Substances 0.000 claims abstract description 16
125000001424 substituent group Chemical group 0.000 claims abstract description 14
239000003960 organic solvent Substances 0.000 claims abstract description 13
239000002841 Lewis acid Substances 0.000 claims abstract description 12
150000007517 lewis acids Chemical class 0.000 claims abstract description 12
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 11
125000005843 halogen group Chemical group 0.000 claims abstract description 9
125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 9
125000002346 iodo group Chemical group I* 0.000 claims abstract description 8
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 7
125000004043 oxo group Chemical group O=* 0.000 claims abstract description 7
125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims abstract description 6
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims abstract description 4
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims abstract description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 97
239000000203 mixture Substances 0.000 claims description 65
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 48
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 33
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 20
125000001153 fluoro group Chemical group F* 0.000 claims description 16
-1 5-fluoropyrimidin-4-yl Chemical group 0.000 claims description 12
MIOPJNTWMNEORI-MHPPCMCBSA-N [(4r)-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methanesulfonic acid Chemical compound C1C[C@]2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-MHPPCMCBSA-N 0.000 claims description 10
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 10
UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 claims description 8
AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 claims description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 claims description 6
235000005074 zinc chloride Nutrition 0.000 claims description 5
239000011592 zinc chloride Substances 0.000 claims description 5
XUJHKPSBHDQIOD-UHFFFAOYSA-N (2-bromo-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methanesulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)C(Br)C1C2(C)C XUJHKPSBHDQIOD-UHFFFAOYSA-N 0.000 claims description 4
229910002651 NO3 Inorganic materials 0.000 claims description 4
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 4
125000000217 alkyl group Chemical group 0.000 claims description 4
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 claims description 4
MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 claims description 4
229910052739 hydrogen Inorganic materials 0.000 claims description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 claims description 4
238000009901 transfer hydrogenation reaction Methods 0.000 claims description 4
MFEDKMBNKNOUPA-UHFFFAOYSA-N (2-bromo-4,7-dimethyl-3-oxo-7-bicyclo[2.2.1]heptanyl)methanesulfonic acid Chemical compound C1CC2(C)C(=O)C(Br)C1C2(CS(O)(=O)=O)C MFEDKMBNKNOUPA-UHFFFAOYSA-N 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 3
229940102001 zinc bromide Drugs 0.000 claims description 3
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 2
229910019142 PO4 Inorganic materials 0.000 claims description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 2
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
229910052763 palladium Inorganic materials 0.000 claims description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
239000010452 phosphate Substances 0.000 claims description 2
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 2
229910021653 sulphate ion Inorganic materials 0.000 claims description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 claims 1
BQDLXFABVRRDFU-XXFAHNHDSA-N (2r,3s)-3-(6-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1,2,4-triazol-1-yl)butan-2-ol Chemical compound C1([C@H](C)[C@](O)(CN2N=CN=C2)C=2C(=CC(F)=CC=2)F)=NC=NC(Cl)=C1F BQDLXFABVRRDFU-XXFAHNHDSA-N 0.000 abstract description 4
HNKWEUANACBPGC-UHFFFAOYSA-N 3-(2,6-dichloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1,2,4-triazol-1-yl)butan-2-ol Chemical compound C1=NC=NN1CC(O)(C=1C(=CC(F)=CC=1)F)C(C)C1=NC(Cl)=NC(Cl)=C1F HNKWEUANACBPGC-UHFFFAOYSA-N 0.000 abstract description 2
UNEWPWKCWOFZPU-UHFFFAOYSA-N 3-(6-chloropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1,2,4-triazol-1-yl)butan-2-ol Chemical compound C1=NC=NN1CC(O)(C=1C(=CC(F)=CC=1)F)C(C)C1=CC(Cl)=NC=N1 UNEWPWKCWOFZPU-UHFFFAOYSA-N 0.000 abstract description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
QGUBIXDOEDZGJI-UHFFFAOYSA-N 3-(2-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1,2,4-triazol-1-yl)butan-2-ol Chemical compound C1=NC=NN1CC(O)(C=1C(=CC(F)=CC=1)F)C(C)C1=NC(Cl)=NC=C1F QGUBIXDOEDZGJI-UHFFFAOYSA-N 0.000 abstract 1
239000000243 solution Substances 0.000 description 87
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 80
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 67
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 41
239000000047 product Substances 0.000 description 40
238000007792 addition Methods 0.000 description 39
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 25
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
238000001914 filtration Methods 0.000 description 24
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
239000010410 layer Substances 0.000 description 19
239000007787 solid Substances 0.000 description 19
238000005160 1H NMR spectroscopy Methods 0.000 description 18
238000004128 high performance liquid chromatography Methods 0.000 description 18
239000003921 oil Substances 0.000 description 17
239000012044 organic layer Substances 0.000 description 16
238000010992 reflux Methods 0.000 description 15
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
ZICDXDPVQDNYTC-UHFFFAOYSA-N butan-2-ol Chemical compound CCC([CH2+])O ZICDXDPVQDNYTC-UHFFFAOYSA-N 0.000 description 14
239000002904 solvent Substances 0.000 description 14
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
XCHRPVARHBCFMJ-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-2-(1,2,4-triazol-1-yl)ethanone Chemical compound FC1=CC(F)=CC=C1C(=O)CN1N=CN=C1 XCHRPVARHBCFMJ-UHFFFAOYSA-N 0.000 description 11
238000001816 cooling Methods 0.000 description 11
239000012074 organic phase Substances 0.000 description 11
239000002002 slurry Substances 0.000 description 11
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 10
239000000284 extract Substances 0.000 description 10
229960000583 acetic acid Drugs 0.000 description 9
239000000706 filtrate Substances 0.000 description 9
239000012258 stirred mixture Substances 0.000 description 9
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
239000000956 alloy Substances 0.000 description 8
229910045601 alloy Inorganic materials 0.000 description 8
238000004821 distillation Methods 0.000 description 8
239000012362 glacial acetic acid Substances 0.000 description 8
229910052751 metal Inorganic materials 0.000 description 8
239000002184 metal Substances 0.000 description 8
229910052757 nitrogen Inorganic materials 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
AAESVRBYUDTWKH-UHFFFAOYSA-N 4-(1-bromoethyl)-6-chloro-5-fluoropyrimidine Chemical compound CC(Br)C1=NC=NC(Cl)=C1F AAESVRBYUDTWKH-UHFFFAOYSA-N 0.000 description 7
230000015572 biosynthetic process Effects 0.000 description 7
239000003054 catalyst Substances 0.000 description 7
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
239000012298 atmosphere Substances 0.000 description 6
238000011065 in-situ storage Methods 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
239000012299 nitrogen atmosphere Substances 0.000 description 6
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical class CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 5
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
239000002585 base Substances 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
238000010438 heat treatment Methods 0.000 description 5
WABPQHHGFIMREM-UHFFFAOYSA-N lead(0) Chemical compound [Pb] WABPQHHGFIMREM-UHFFFAOYSA-N 0.000 description 5
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 5
239000004296 sodium metabisulphite Substances 0.000 description 5
235000010262 sodium metabisulphite Nutrition 0.000 description 5
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
238000004458 analytical method Methods 0.000 description 4
239000008346 aqueous phase Substances 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
239000012071 phase Substances 0.000 description 4
229910000029 sodium carbonate Inorganic materials 0.000 description 4
239000007858 starting material Substances 0.000 description 4
238000003756 stirring Methods 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
239000006188 syrup Substances 0.000 description 4
235000020357 syrup Nutrition 0.000 description 4
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
ZXMSBCQGASSUBH-UHFFFAOYSA-N 3-benzyl-6-(1-bromoethyl)-5-fluoropyrimidin-4-one Chemical compound O=C1C(F)=C(C(Br)C)N=CN1CC1=CC=CC=C1 ZXMSBCQGASSUBH-UHFFFAOYSA-N 0.000 description 3
KSXLAAMIXVHNJJ-UHFFFAOYSA-N 4-(1-bromoethyl)-6-chloropyrimidine Chemical compound CC(Br)C1=CC(Cl)=NC=N1 KSXLAAMIXVHNJJ-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
OVBJJZOQPCKUOR-UHFFFAOYSA-L EDTA disodium salt dihydrate Chemical compound O.O.[Na+].[Na+].[O-]C(=O)C[NH+](CC([O-])=O)CC[NH+](CC([O-])=O)CC([O-])=O OVBJJZOQPCKUOR-UHFFFAOYSA-L 0.000 description 3
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
150000001299 aldehydes Chemical class 0.000 description 3
239000012267 brine Substances 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
239000012043 crude product Substances 0.000 description 3
238000010908 decantation Methods 0.000 description 3
238000001035 drying Methods 0.000 description 3
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
229910000041 hydrogen chloride Inorganic materials 0.000 description 3
229910052744 lithium Inorganic materials 0.000 description 3
235000019341 magnesium sulphate Nutrition 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
239000011734 sodium Substances 0.000 description 3
150000003509 tertiary alcohols Chemical class 0.000 description 3
125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 description 2
BDOYKFSQFYNPKF-UHFFFAOYSA-N 2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid;sodium Chemical compound [Na].[Na].OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O BDOYKFSQFYNPKF-UHFFFAOYSA-N 0.000 description 2
BQDLXFABVRRDFU-UHFFFAOYSA-N 3-(6-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1,2,4-triazol-1-yl)butan-2-ol Chemical compound C1=NC=NN1CC(O)(C=1C(=CC(F)=CC=1)F)C(C)C1=NC=NC(Cl)=C1F BQDLXFABVRRDFU-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
239000007818 Grignard reagent Substances 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
FMRLDPWIRHBCCC-UHFFFAOYSA-L Zinc carbonate Chemical compound [Zn+2].[O-]C([O-])=O FMRLDPWIRHBCCC-UHFFFAOYSA-L 0.000 description 2
150000003863 ammonium salts Chemical class 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
238000003556 assay Methods 0.000 description 2
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 2
BJDCWCLMFKKGEE-CMDXXVQNSA-N chembl252518 Chemical compound C([C@@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@H](O)[C@@H]4C BJDCWCLMFKKGEE-CMDXXVQNSA-N 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
239000013078 crystal Substances 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
238000001640 fractional crystallisation Methods 0.000 description 2
239000012458 free base Substances 0.000 description 2
150000004795 grignard reagents Chemical class 0.000 description 2
150000004820 halides Chemical class 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
230000014759 maintenance of location Effects 0.000 description 2
239000000463 material Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
239000011591 potassium Substances 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
239000001632 sodium acetate Substances 0.000 description 2
235000017281 sodium acetate Nutrition 0.000 description 2
235000004416 zinc carbonate Nutrition 0.000 description 2
239000011667 zinc carbonate Substances 0.000 description 2
229910000010 zinc carbonate Inorganic materials 0.000 description 2
HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
RXGNQUOYJPSWRW-UHFFFAOYSA-N 1-phenyl-2-(1,2,4-triazol-1-yl)ethanone Chemical class C=1C=CC=CC=1C(=O)CN1C=NC=N1 RXGNQUOYJPSWRW-UHFFFAOYSA-N 0.000 description 1
FXKZPKBFTQUJBA-UHFFFAOYSA-N 2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid;sodium;dihydrate Chemical compound O.O.[Na].[Na].OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O FXKZPKBFTQUJBA-UHFFFAOYSA-N 0.000 description 1
WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 1
GRYASYLFKKQPPF-UHFFFAOYSA-N 2-chloro-6-ethyl-5-fluoro-1h-pyrimidin-4-one Chemical compound CCC1=NC(Cl)=NC(O)=C1F GRYASYLFKKQPPF-UHFFFAOYSA-N 0.000 description 1
BHDKTFQBRFWJKR-UHFFFAOYSA-N 2-hydroxy-5-sulfobenzoic acid;dihydrate Chemical compound O.O.OC(=O)C1=CC(S(O)(=O)=O)=CC=C1O BHDKTFQBRFWJKR-UHFFFAOYSA-N 0.000 description 1
BYPQMBZXTZGDEP-UHFFFAOYSA-N 3-benzyl-6-[3-(2,4-difluorophenyl)-3-hydroxy-4-(1,2,4-triazol-1-yl)butan-2-yl]-5-fluoropyrimidin-4-one Chemical compound C1=NC=NN1CC(O)(C=1C(=CC(F)=CC=1)F)C(C)C(=C(C1=O)F)N=CN1CC1=CC=CC=C1 BYPQMBZXTZGDEP-UHFFFAOYSA-N 0.000 description 1
AZJXRKANGIKJQD-UHFFFAOYSA-N 4-(1-bromoethyl)-2,6-dichloro-5-fluoropyrimidine Chemical compound CC(Br)C1=NC(Cl)=NC(Cl)=C1F AZJXRKANGIKJQD-UHFFFAOYSA-N 0.000 description 1
HNRVNZSHWCXVSQ-UHFFFAOYSA-N 4-(1-bromoethyl)-2-chloro-5-fluoropyrimidine Chemical compound CC(Br)C1=NC(Cl)=NC=C1F HNRVNZSHWCXVSQ-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
229910015900 BF3 Inorganic materials 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 description 1
238000007259 addition reaction Methods 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
239000004411 aluminium Substances 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
235000011114 ammonium hydroxide Nutrition 0.000 description 1
230000000843 anti-fungal effect Effects 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
238000010533 azeotropic distillation Methods 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
IFMWVBVPVXRZHE-UHFFFAOYSA-M chlorotitanium(3+);propan-2-olate Chemical compound [Cl-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-] IFMWVBVPVXRZHE-UHFFFAOYSA-M 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000002274 desiccant Substances 0.000 description 1
YNLAOSYQHBDIKW-UHFFFAOYSA-M diethylaluminium chloride Chemical compound CC[Al](Cl)CC YNLAOSYQHBDIKW-UHFFFAOYSA-M 0.000 description 1
UZUODNWWWUQRIR-UHFFFAOYSA-L disodium;3-aminonaphthalene-1,5-disulfonate Chemical compound [Na+].[Na+].C1=CC=C(S([O-])(=O)=O)C2=CC(N)=CC(S([O-])(=O)=O)=C21 UZUODNWWWUQRIR-UHFFFAOYSA-L 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
RMGVZKRVHHSUIM-UHFFFAOYSA-L dithionate(2-) Chemical compound [O-]S(=O)(=O)S([O-])(=O)=O RMGVZKRVHHSUIM-UHFFFAOYSA-L 0.000 description 1
229960002949 fluorouracil Drugs 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000000852 hydrogen donor Substances 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
239000012535 impurity Substances 0.000 description 1
RQQRAHKHDFPBMC-UHFFFAOYSA-L lead(ii) iodide Chemical compound I[Pb]I RQQRAHKHDFPBMC-UHFFFAOYSA-L 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
XJMIXEAZMCTAGH-UHFFFAOYSA-N methyl 3-oxopentanoate Chemical compound CCC(=O)CC(=O)OC XJMIXEAZMCTAGH-UHFFFAOYSA-N 0.000 description 1
238000005935 nucleophilic addition reaction Methods 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
WFIZEGIEIOHZCP-UHFFFAOYSA-M potassium formate Chemical compound [K+].[O-]C=O WFIZEGIEIOHZCP-UHFFFAOYSA-M 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
239000000843 powder Substances 0.000 description 1
150000003230 pyrimidines Chemical class 0.000 description 1
229910052703 rhodium Inorganic materials 0.000 description 1
239000010948 rhodium Substances 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
150000003333 secondary alcohols Chemical class 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000000758 substrate Substances 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000011135 tin Substances 0.000 description 1
229910052718 tin Inorganic materials 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
BCEHBSKCWLPMDN-MGPLVRAMSA-N voriconazole Chemical compound C1([C@H](C)[C@](O)(CN2N=CN=C2)C=2C(=CC(F)=CC=2)F)=NC=NC=C1F BCEHBSKCWLPMDN-MGPLVRAMSA-N 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/30—Halogen atoms or nitro radicals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/34—One oxygen atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/34—One oxygen atom
- C07D239/36—One oxygen atom as doubly bound oxygen atom or as unsubstituted hydroxy radical
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Epidemiology (AREA)
Plural Heterocyclic Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)

IL12246296A 1995-08-05 1996-07-26 Preparation of triazoles by organometallic metal attachment to ketones and a number of such new compounds IL122462A (en)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
IL13152196A IL131521A (en)	1995-08-05	1996-07-26	History of pyrimidine

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9516121.2A GB9516121D0 (en)	1995-08-05	1995-08-05	Organometallic addition to ketones
PCT/EP1996/003376 WO1997006160A1 (en)	1995-08-05	1996-07-26	Preparation of triazoles by organometallic addition to ketones and intermediates therefor

Publications (2)

Publication Number	Publication Date
IL122462A0 IL122462A0 (en)	1998-06-15
IL122462A true IL122462A (en)	2001-10-31

Family

ID=10778850

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
IL12246296A IL122462A (en)	1995-08-05	1996-07-26	Preparation of triazoles by organometallic metal attachment to ketones and a number of such new compounds
IL13152196A IL131521A (en)	1995-08-05	1996-07-26	History of pyrimidine

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
IL13152196A IL131521A (en)	1995-08-05	1996-07-26	History of pyrimidine

Country Status (31)

Country	Link
US (2)	US6586594B1 (de)
EP (1)	EP0871625B1 (de)
JP (3)	JP3211965B2 (de)
KR (1)	KR100269048B1 (de)
CN (1)	CN1076019C (de)
AR (1)	AR003472A1 (de)
AT (1)	ATE256679T1 (de)
AU (1)	AU703337B2 (de)
BR (1)	BR9609960A (de)
CA (1)	CA2228655C (de)
CZ (1)	CZ296975B6 (de)
DE (1)	DE69631160T2 (de)
DK (1)	DK0871625T3 (de)
EG (1)	EG21200A (de)
ES (1)	ES2210382T3 (de)
GB (1)	GB9516121D0 (de)
HU (1)	HU224339B1 (de)
IL (2)	IL122462A (de)
IN (1)	IN190817B (de)
MX (1)	MX9801025A (de)
MY (1)	MY123062A (de)
NO (1)	NO314938B1 (de)
NZ (1)	NZ315651A (de)
PE (1)	PE16897A1 (de)
PL (1)	PL187227B1 (de)
PT (1)	PT871625E (de)
RU (1)	RU2156760C2 (de)
TR (1)	TR199800170T1 (de)
TW (1)	TW442480B (de)
WO (1)	WO1997006160A1 (de)
ZA (1)	ZA966587B (de)

Families Citing this family (48)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7193083B2 (en) *	1996-07-26	2007-03-20	Pfizer, Inc.	Preparation of triazoles by organometallic addition to ketones and intermediates therefor
TWI329105B (en)	2002-02-01	2010-08-21	Rigel Pharmaceuticals Inc	2,4-pyrimidinediamine compounds and their uses
HRP20050089B1 (hr)	2002-07-29	2015-06-19	Rigel Pharmaceuticals	Upotreba 2,4 pirimidindiaminskog spoja za proizvodnju lijeka za lijeäśenje ili sprjeäśavanje autoimunosne bolesti
WO2005012294A1 (en)	2003-07-30	2005-02-10	Rigel Pharmaceuticals, Inc.	2,4-pyrimidinediamine compounds for use in the treatment or prevention of autoimmune diseases
JP2008511659A (ja) *	2004-09-01	2008-04-17	ライジェルファーマシューティカルズ，インコーポレイテッド	２，４−ピリミジンジアミン化合物の合成
SI1814878T1 (sl)	2004-11-24	2012-06-29	Rigel Pharmaceuticals Inc	Spojine spiro-2,4-pirimidindiamina in njihova uporaba
CA2590687C (en) *	2004-12-14	2013-09-10	Dr. Reddy's Laboratories Ltd.	Process for preparing voriconazole
EP1883302A4 (de) *	2005-05-03	2009-05-20	Rigel Pharmaceuticals Inc	Jak-kinase-hemmer und deren verwendung
WO2007132354A2 (en) *	2006-02-01	2007-11-22	Medichem, S.A.	Process for preparing voriconazole, new polymorphic form of intermediate thereof, and uses thereof
AR061889A1 (es)	2006-07-13	2008-10-01	Medichem Sa	Proceso mejorado para la preparacion de voriconazol
CN1919846B (zh) *	2006-09-14	2013-01-02	大道隆达（北京）医药科技发展有限公司	伏立康唑及其药用盐、中间体的一种新定向合成制备方法
KR100889937B1 (ko) *	2007-08-06	2009-03-20	한미약품 주식회사	보리코나졸의 제조방법
GB2452049A (en) *	2007-08-21	2009-02-25	Alpharma Aps	Process for the preparation of voriconazole
WO2009084029A2 (en) *	2007-12-03	2009-07-09	Neuland Laboratories Ltd	Improved process for the preparation of (2r,3s)-2-(2,4- difluqrophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1h-1,2,4-triazol-1-yl) butan-2-ol
CN101575330B (zh) *	2008-05-05	2012-10-31	丽珠医药集团股份有限公司	伏立康唑广谱抗真菌药物化合物、其组合物及用途
RU2393158C1 (ru) *	2008-10-06	2010-06-27	Андрей Александрович Иващенко	ЗАМЕЩЕННЫЕ 3-АРИЛСУЛЬФОНИЛ-ПИРАЗОЛО[1,5-а]ПИРИМИДИНЫ, АНТАГОНИСТЫ СЕРОТОНИНОВЫХ 5-HT6 РЕЦЕПТОРОВ, СПОСОБЫ ИХ ПОЛУЧЕНИЯ И ПРИМЕНЕНИЯ
RU2399621C2 (ru) *	2008-10-14	2010-09-20	Андрей Александрович Иващенко	ЗАМЕЩЕННЫЕ 2-АЛКИЛАМИНО-3-СУЛЬФОНИЛ-ПИРАЗОЛО[1,5-a]ПИРИМИДИНЫ, АНТАГОНИСТЫ СЕРОТОНИНОВЫХ 5-HT6 РЕЦЕПТОРОВ, СПОСОБЫ ИХ ПОЛУЧЕНИЯ И ПРИМЕНЕНИЯ
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US20030181720A1 (en)	2003-09-25
PL187227B1 (pl)	2004-06-30
US6586594B1 (en)	2003-07-01
JP2001354670A (ja)	2001-12-25
CZ32798A3 (cs)	1999-03-17
PT871625E (pt)	2004-04-30
DK0871625T3 (da)	2004-03-29
KR100269048B1 (ko)	2000-10-16
JP3224532B2 (ja)	2001-10-29
DE69631160T2 (de)	2004-07-08
NO314938B1 (no)	2003-06-16
RU2156760C2 (ru)	2000-09-27
ZA966587B (en)	1998-02-02
PE16897A1 (es)	1997-05-21
IL122462A0 (en)	1998-06-15
IL131521A (en)	2001-08-08
ES2210382T3 (es)	2004-07-01
EG21200A (en)	2001-01-31
HUP9802766A2 (hu)	1999-02-01
BR9609960A (pt)	1999-02-02
IL131521A0 (en)	2001-01-28
DE69631160D1 (de)	2004-01-29
CN1195346A (zh)	1998-10-07
PL324922A1 (en)	1998-06-22
CZ296975B6 (cs)	2006-08-16
MX9801025A (es)	1998-04-30
CN1076019C (zh)	2001-12-12
AU703337B2 (en)	1999-03-25
HU224339B1 (hu)	2005-08-29
TW442480B (en)	2001-06-23
JP3211965B2 (ja)	2001-09-25
JP2001026583A (ja)	2001-01-30
EP0871625B1 (de)	2003-12-17
NO980441D0 (no)	1998-02-02
JPH10510549A (ja)	1998-10-13
CA2228655A1 (en)	1997-02-20
KR19990036174A (ko)	1999-05-25
ATE256679T1 (de)	2004-01-15
HK1014944A1 (en)	1999-10-08
GB9516121D0 (en)	1995-10-04
WO1997006160A1 (en)	1997-02-20
AR003472A1 (es)	1998-08-05
CA2228655C (en)	2003-09-09
NZ315651A (en)	1999-03-29
US6946555B2 (en)	2005-09-20
HUP9802766A3 (en)	2000-03-28
IN190817B (de)	2003-08-23
NO980441L (no)	1998-03-26
EP0871625A1 (de)	1998-10-21
TR199800170T1 (xx)	1998-06-22
MY123062A (en)	2006-05-31
AU6740396A (en)	1997-03-05

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